Assessment of cerebrospinal fluid (CSF) beta-amyloid (1-42), phosphorylated tau (ptau-181) and total Tau protein in patients with Alzheimer's disease (AD) and other dementia at Siriraj Hospital, Thailand.

BACKGROUND: The combination of decreased cerebrospinal fluid (CSF) levels of beta-amyloid (1-42) and increased levels of phosphorylated tau (ptau-181) or total tau protein are known to be biomarkers ofAlzheimer's disease (AD). These biomarkers can also be used as predictors of disease progression in persons with mild cognitive impairment. Utilizing biomarkers to differentiate Alzheimer's disease (AD) against non-Alzheimer dementia (non-AD) needs to be explored.

OBJECTIVE: To evaluate the clinical use ofCSF biomarker: beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein for distinguishing Alzheimer's disease (AD) from non-Alzheimer dementia (non-AD) in Thai patients.

MATERIAL AND METHOD: Thirty patients diagnosed of dementia during 2005-2007 at Siriraj hospital were offered CSF analysis for beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein. Diagnosis of dementia was performed by a concensus diagnostic group utilizing a standard criteria for diagnosis of AD and other dementia. All CSF testing was performed by Enzyme-Linked Immunoassay (ELISA) technique of the INNOTESTM to analyze these biomarkers.

RESULTS: Thirty demented patients were recruited in the study. Fourteen had AD and 16 had non-AD including 5 vascular dementia, 5 normal pressure hydrocephalus, 4 frontotemporal lobar degeneration and others. Mean age of the AD group was 67.79 (12.30) and that of non-AD group was 65.75 (15.04). Twelve AD had decreased levels of CSF /3-amyloid (1-42) (less than 487 pg/ml). Only one patient with AD had increased CSF phosphorylated tau (ptau-181) (more than 61 pg/ml). None of theAD patient had increased CSF total tau (more than 425 pg/ml). Eight patients with non-AD had decreased levels of CSF p-amyloid (1-42), one had increased CSF total tau protein, and none had increased CSF phosphorylated tau (ptau-181) protein. The sensitivity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 85.71%. Those of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 7.14% and 0% consecutively. The specificity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 50%. The specificity of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 100% and 93.75% sequentially. The combination of 2 biomarkers would increase specificity but decrease sensitivity.

CONCLUSION: CSF biomarker analysis should be encouraged to use as diagnostic aid in memory clinic especially to help diagnosis of atypical presentation of AD. The usefulness of longitudinal data needs to be explored.